Seroprevalence of Hepatitis A among Different Age Groups in Sakarya and Review of The Literature

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1 110 Research Article Doi: /vhd Viral Hepatitis Journal 2014; 20(3): Seroprevalence of Hepatitis A among Different Age Groups in Sakarya and Review of The Literature Farklı Yaş Gruplarında Hepatit A Seroprevalansı; Sakarya Verileri ve Literatür Derlemesi Mehmet Köroğlu1,2, Tayfur Demİray2, Hüseyin Agah Terzİ2, Mustafa Altındİş1,2 1 Sakarya University Faculty of Medicine, Department of Clinical Microbiology, Sakarya, Turkey 2 Sakarya Training and Research Hospital, Clinic of Clinical Microbiology, Sakarya, Turkey ABSTRACT Objectıves: The aim of this study was to investigate the seroprevalence of hepatitis A virus (HAV) infection in all age groups in Sakarya province and to review previously presented data about HAV seroprevalence in Turkey. Materials and Methods: We retrospectively evaluated the records of patients who were tested for IgG anti-hav and Igm anti-hav for diagnostic and screening purposes between of and Anti-HAV antibodies in serum samples were analyzed with chemiluminescence microparticle immunoassay (CMI) method (Architect i2000, Abbott). Values below 1 s/co were accepted as negative and values 1 s/co were considered positive. Results: IgG anti-hav positivity was determined in 1498 (74.7%) people out of 2003 for the two-year screening period. Positivity rates were found as 29.7%, 43.4%, 57.1%, 84.8%, 96.8%, 99%, and 99.3% in the age groups 0-10, 11-20, 21-30, 31-40, 41-50, and 61-92, respectively. IgM anti-hav positivity was detected in 75 (4.44%) of 1693 people. IgM anti-hav positivity rates according to age groups 0-10, 11-20, 21-30, 31-40, 41-50, 51-60, and years were 13.2%, 13.7%, 6.3%, 1%, 0%, 0%, and 0.6%, respectively. Conclusion: Our study provides information about the serological status of HAV in Sakarya. Knowledge of the seroprevalence of hepatitis A virus will be guiding for establishing appropriate preventive measures and creation of vaccination programs. Besides the use of vaccines, sanitation activities, creation of healthy water sources, and improving infrastructure systems will make significant contribution toward reducing the incidence of HAV infection. The data obtained from this and similar studies will provide the opportunity to examine and compare the results of the routine HAV vaccination in the forthcoming years. (Viral Hepatitis Journal 2014; 20(3): ) Key words: Hepatitis A, anti-hav, IgG anti-hav, IgM anti-hav, seroprevalence, hepatitis A vaccine Conflict of interest: The authors reported no conflict of interest related to this article. ÖZET Amaç: Bu çalışmada Sakarya ilinde tüm yaş grupları için Hepatit A virus (HAV) enfeksiyonunun seroprevalansının araştırılması ve ülkemize ait daha önce yayınlanmış verilerin derlenmesi amaçlanmıştır. Gereç ve Yöntemler: Çalışmamızda ile tarihleri arasında tanı ve tarama amaçlı anti-hav IgG ve anti-hav IgM testi istenen hastalara ait kayıtlar retrospektif olarak incelenmiştir. Anti-HAV antikorlarının varlığı kemiluminesens mikropartikül immunoassay (CMIA) yöntemi ile (Architect i2000, Abbott) çalışılmıştır. Bir s/co altındaki değerlere sahip numuneler negatif ve 1 s/co değerlerine sahip örnekler pozitif olarak değerlendirilmiştir. Bulgular: İki yıllık sürede tarama yapılan 2,003 kişiden 1,498 inde (%74,7) anti-hav IgG pozitifliği saptanmıştır. Sıfır-10 yaş grubunda %29,7, yaş grubunda %43,4, yaş grubunda % 57,1, yaş grubunda %84,8, yaş grubunda %96,8, yaş grubunda %99 ve yaş grubunda %99,3 oranında anti-hav IgG pozitif bulunmuştur. Anti-HAV IgM pozitifliği, çalışma kapsamındaki 1,693 kişiden 75 inde (%4,44) saptanmıştır. Yaş gruplarına göre anti-hav IgM pozitifliği ise 0-10 yaş %12,1, yaş %15,9, yaş %6,9, yaş %1,7, yaş %0,5, yaş %0,6 ve 60 yaş üstünde %1,2 olarak saptanmıştır. Sonuç: Çalışma, Sakarya ilinin HAV yönünden serolojik durumu hakkında bilgi vermektedir. Hepatit A virüsünün prevalansının bilinmesi hastalık için uygun koruyucu önlemlerin alınabilmesinde ve aşı programlarının oluşturulmasında yol gösterici olacaktır. Aşı kullanımının yanında, sanitasyon çalışmaları, sağlıklı su kaynaklarının ulaşılabilir hale getirilmesi ve kanalizasyon-alt yapı çalışmalarına ağırlık verilmesi de HAV enfeksiyonları sıklığını azaltacaktır. Bu ve benzeri çalışmalardan elde edilen veriler, ilerleyen yıllarda rutin HAV aşı uygulamasının sonuçlarını incelemek amacıyla yapılacak araştırmalara katkı ve mukayese imkanı sağlayacaktır. (Viral Hepatit Dergisi 2014; 20(3): ) Anahtar kelimeler: Hepatit A, anti-hav, anti-hav IgG, anti-hav IgM, seroprevalans, hepatit A aşısı Çıkar çatışması: Yazarlar bu makale ile ilgili olarak herhangi bir çıkar çatışması bildirmemişlerdir. Address for Correspondence: Tayfur Demiray MD, Sakarya Training and Research Hospital, Clinic of Clinical Microbiology, Sakarya, Turkey Gsm: tayfurdemiray@gmail.com Received: Accepted: Viral Hepatitis Journal, pub lis hed by Ga le nos Pub lis hing.

2 Köroğlu et al. 111 Introduction Hepatitis A virus (HAV) infection that is characterized by primary inflammation of the liver causes a self-limited, nonchronic disease (1). The fecal-oral route is the primary mode of transmission since a high amount of virus is excreted by an infected person. Also, person-to-person contact, ingestion of contaminated food and water, and spread between people in the same house are other ways of transmission (2). 70% of HAV infections are asymptomatic and not accompanied by jaundice in children under five years of age, however, in adults and older children, infection is symptomatic with jaundice occurring in 70% of patients. Less than 1% of patients develop fulminant hepatitis. Fulminant disease due to hepatitis A is more likely to resolve spontaneously than fulminant diseases of other viral etiologies (3). IgG anti-hav and IgM antibodies are investigated for the diagnosis. The virus has 4 genotypes capable of infecting humans and has only one serotype. IgG anti-hav, which appears early in the course of infection, provides lifetime protection against the disease. Determination of IgG anti-hav is a method commonly used in prevalence studies. The aim of this study was to determine the distribution of IgG anti-hav and IgM seropositivity rates in different age groups. Materials and Methods We retrospectively evaluated the records of patients who were tested for IgG anti-hav and IgM anti-hav seropositivity for diagnostic and screening purposes in Sakarya University Training and Research Hospital between of and Blood samples from patients were separated by centrifugation and anti-hav antibodies in serum samples were analyzed with chemiluminescence microparticle immunoassay (CMIA) method (Architect i2000, Abbott, USA). Repeating samples were excluded from the study. S/Co values of less than 1 were accepted as negative; and s/co values of more than 1 were considered positive according to manufacturer s instructions. For statistical evaluation, SPSS 21.0 program (IBM inc, Chicago, USA) was used and one-way ANOVA test was performed. A p value of less than 0.05 was considered statistically significant. Results In the two-year screening period, out of 2.003, 1498 (74.7%) subjects were found to be positive for IgG anti-hav. Of the positive patients, 39% were female (n=782) and 35.7% were male. Positivity rates are presented in Table 1. In this study, IgG anti-hav positivity rate was observed as more than 96% in the groups over 41 years of age. IgG anti HAV seropositivity in 0-10, and age groups were significantly lower compared to 31-40, 41-50, and age groups (p<0.001). There was no statistically significant difference between the other age groups. IgM anti-hav positivity was detected in 75 (4.44%) of 1693 people. IgM anti-hav positivity rates in the age groups 0-10, 11-20, 21-30, 31-40, 41-50, 51-60, and years were 13.2%, 13.7%, 6.3%, 1%, 0%, 0%, and 0.6%, respectively. The highest IgM anti-hav positivity was seen in the years age group (Table 2). IgM anti-hav seropositivity rates in 0-10, and age groups were significantly higher compared to 31-40, 41-50, and age groups (p<0.001). There was no statistically significant difference between the other age groups. Discussion HAV infection is detected in all over the world. It is common in developing countries and like other enteric virus infections, is one of the typical diseases of childhood (4). The infection usually takes place during childhood period in developing countries, due to fecal-oral transmission in consequence of insufficient infrastructure and sewage services, and contaminated water supplies. In general, in countries with higher socioeconomic levels, HAV infections are encountered in older age groups. It has been demonstrated that, the reduction in the number of cases in these countries may be attributed to improved hygiene and sanitation conditions in addition to routine vaccination (3,5). Turkey is in a middle endemic region according to the epidemiological data of HAV infections. The seroprevalence of HAV infection differs among various regions of the country. Ceyhan et al. detected HAV seroprevalence in the central and the western regions of the country as moderate, whereas HAV seroprevalence was high in the eastern and southern parts (6,7). Noteworthy, it has been shown that seropositivity rates in different regions, sometimes within the same province and even within different residential areas could differ (8,9). Data about the distribution of HAV seropositivity, collected from several publications conducted in Turkey according to age groups, between the years of , are given in Table 3. It is clear that hepatitis A virus is still endemic and widespread in our country as stated in many previously conducted studies. Western regions, where socioeconomic levels higher and more developed in terms of hygiene and sanitation conditions, it is observed that the age distribution shifts toward adolescents and young adulthoods (10). In this regard, an adult group who are prone to HAV infection has been reported (11,12). With advancing age, the risk of HAV infection as well as likelihood of complicated clinical course increases (4). According to the Centers for Disease Control and Prevention, USA (CDC), the overall case-fatality ratio of HAV infections is 3%, this ratio is 1.8% in adults older than 50 years of age (13). In this study, in concordance with the previous ones, seropositivity of HAV gradually increases with age (Table 1, 2). Similar data have been reported in different areas of the world. In a study conducted in Korea, it was stated that the incidence of HAV infection in the age group over 30 years has increased from 15.2% in the years between 1995 and 1999, to 28.4% in the years between 2000 and 2005 (14). The incidence rate was almost doubled,

3 112 Köroğlu et al. thus, this situation was interpreted as a population in the adult age group was formed, who were susceptible to HAV infection and this specific group should be protected. These findings emphasize the importance of researches including of all age groups. In studies performed in different regions of Turkey, the seroprevalence in children has been reported to vary between 35% and 80% (15). Çopur et al. reported that the prevalence of IgG anti-hav IgG among children was 29.5% (16). In our study, the rate in children was found to be 29.7%. As stated in recent studies performed on pediatric age group, seropositivity rates have started to decline (Table 1, 2). These findings may be considered as the result of improvements in hygiene and sanitation conditions, as well as routine immunization. Routine infant hepatitis A vaccination for hepatitis A has been taken to the vaccination schedules in our country by the Table 1. Serological profile of IgG anti-hepatitis A virus antibody according to age groups Age Group Anti-Hepatitis A Virus IgG Positive Male % Female % 0-10 (n=128) (n=265) (n=445) (n=400) (n=283) (n=200) (n=282) Total (n=2003) Total Positivity (%) year In addition, HAV seronegative health care workers who work in high-risk departments are being vaccinated. Hepatitis A immunization is determined by factors such as age and anti-hav seroprevalence (10). Children are very contagious and may spread the virus to individuals in all age groups. Therefore, vaccination in this group will contribute to immunity in the whole society and the protection of unvaccinated persons (17). By the routine administration of hepatitis A vaccine in the United States, the incidence of HAV infection has dropped from cases annually in 1997 to 8795 cases in 2002 (18). Studies performed on adult population in different years and regions in our country demonstrated different results (Table 3). In a study conducted in the Çanakkale Providence, the prevalence rate was 78.2% in 0-91 age group (19). A multicenter study, determined the prevalence as 74% (20). In the literature, HAV positivity in adult patients has been reported Table 2. Serological profile of IgM anti-hepatitis A virus antibody according to age groups Anti-Hepatitis A Virus IgM Positive Total Age Group Positivity Male % Female % (%) 0-10 (n=159) (n=196) (n=344) (n=289) (n=193) (n=169) (n=343) Total (n=1693) Table 3. Distribution of hepatitis A virus seropositivity in different parts of the Turkey Study Year Providence/City Age Number Anti-Hepatitis A Virus IgG Seropositivity (%) Arabacı, (19) 2009 Çanakkale Turker, (22) Multicenter Çetinkol, (27) 2011 Ünye Tosun, (24) 2011 Multicenter <20, > Altuntaş, (25) Haseki Karakaş, (26) 2012 Ankara Ertürk, (4) 2012 Rize This Study 2014 Sakarya Tosun, (20) Multicenter Tekay, (11) Hakkari Aslan, (28) Gaziantep Arvas, (29) 2011 Iğdır Okur, (30) 2011 Van

4 Köroğlu et al. 113 to be between 88.8% and 100% (21). Recent studies reported seropositivity rates varying between 75% and 96.8% in adults (people older than 15 years of age) (4,22). In our study, we found that the seropositivity rate was 87.4% in individuals between 21 and 92 years of age. In the age group 21-30, the rate was 57.1% and the highest rates range from 84.8% to 99.3% in age groups (Table 1). There was a significant increase in seropositivity rate after 30 years of age. These data showed that the age distribution shifted toward advanced ages. We determined nearly the same results with a recent study conducted by Alıcı et al. in It was stated that after the fourth decade of life, seropositivity increased over 90% (23). Hepatitis A infection is the problem of developing countries, especially when infrastructure and sewage services are inadequate and water sources are contaminated. Domestic migrations and foreign migrations due to war are so intense even in our city, that enough attention should be paid to avoid outbreaks especially for the other diseases transmitted by fecal-oral route together with hepatitis A. Improvements in socioeconomic and hygienic conditions decrease the HAV infection incidence. However the importance of active immunization is increasing not only in the adult population but also in high-risk groups due to higher morbidity and mortality at later ages (20). In areas with a high proportion of susceptible adult population, appropriate vaccination programs should be implemented at least in the high-risk groups, such as healthcare professionals, sewage workers, soldiers, workers in the food industry, people with chronic hepatitis B and C, drug addicts, and etc. An important and remarkable determination should be mentioned that there are differences in many studies conducted in Turkey in aspect of the age groups. Since age groups were not homologous, effective comparisons and evaluations within the age groups between data from different studies cannot be established. Standardization of age groups in prevalence researches will provide efficient use of the data. Our study provides information about the serological status of HAV in Sakarya. Knowledge of the seroprevalence of hepatitis A virus will be guiding for establishing appropriate preventive measures and creation of vaccination programs. Besides the use of vaccines, sanitation activities, creation of healthy water sources, improving infrastructure systems will make significant contribution toward reducing the incidence of HAV infection. The data obtained in this and similar studies will provide an opportunity to examine the effectiveness of routine HAV vaccination. References 1. Curry MP, Chopra S. Acute Viral Hepatitis. In: Mandell GL, Bennett JE, Dolin R (eds.), Principles and Practice of Infectious Diseases. 6 st ed. 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